Biosynthesis and biology of mammalian GPI-anchored proteins

Open Biol. 2020 Mar;10(3):190290. doi: 10.1098/rsob.190290. Epub 2020 Mar 11.


At least 150 human proteins are glycosylphosphatidylinositol-anchored proteins (GPI-APs). The protein moiety of GPI-APs lacking transmembrane domains is anchored to the plasma membrane with GPI covalently attached to the C-terminus. The GPI consists of the conserved core glycan, phosphatidylinositol and glycan side chains. The entire GPI-AP is anchored to the outer leaflet of the lipid bilayer by insertion of fatty chains of phosphatidylinositol. Because of GPI-dependent membrane anchoring, GPI-APs have some unique characteristics. The most prominent feature of GPI-APs is their association with membrane microdomains or membrane rafts. In the polarized cells such as epithelial cells, many GPI-APs are exclusively expressed in the apical surfaces, whereas some GPI-APs are preferentially expressed in the basolateral surfaces. Several GPI-APs act as transcytotic transporters carrying their ligands from one compartment to another. Some GPI-APs are shed from the membrane after cleavage within the GPI by a GPI-specific phospholipase or a glycosidase. In this review, I will summarize the current understanding of GPI-AP biosynthesis in mammalian cells and discuss examples of GPI-dependent functions of mammalian GPI-APs.

Keywords: GPI deficiency; biosynthetic pathway; glycosylphosphatidylinositol; post-translational modification; protein shedding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Cell Membrane / metabolism*
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / chemistry
  • GPI-Linked Proteins / metabolism*
  • Humans
  • Lipid Metabolism


  • GPI-Linked Proteins